Genome-wide association study of blood pressure and hypertension

Daniel Levy, Georg B. Ehret, Kenneth Rice, Germaine C. Verwoert, Lenore J. Launer, Abbas Dehghan, Nicole L. Glazer, Alanna C. Morrison, Andrew D. Johnson, Thor Aspelund, Yurii Aulchenko, Thomas Lumley, Anna Köttgen, Ramachandran S. Vasan, Fernando Rivadeneira, Gudny Eiriksdottir, Xiuqing Guo, Dan E. Arking, Gary F. Mitchell, Francesco U.S. Mattace-RasoAlbert V. Smith, Kent Taylor, Robert B. Scharpf, Shih Jen Hwang, Eric J.G. Sijbrands, Joshua Bis, Tamara B. Harris, Santhi K. Ganesh, Christopher J. O'Donnell, Albert Hofman, Jerome I. Rotter, Josef Coresh, Emelia J. Benjamin, André G. Uitterlinden, Gerardo Heiss, Caroline S. Fox, Jacqueline C.M. Witteman, Eric Boerwinkle, Thomas J. Wang, Vilmundur Gudnason, Martin G. Larson, Aravinda Chakravarti, Bruce M. Psaty, Cornelia M. Van Duijn

Research output: Contribution to journalArticle

956 Scopus citations

Abstract

Blood pressure is a major cardiovascular disease risk factor. To date, few variants associated with interindividual blood pressure variation have been identified and replicated. Here we report results of a genome-wide association study of systolic (SBP) and diastolic (DBP) blood pressure and hypertension in the CHARGE Consortium (n = 29,136), identifying 13 SNPs for SBP, 20 for DBP and 10 for hypertension at P 4 × 10 7. The top ten loci for SBP and DBP were incorporated into a risk score; mean BP and prevalence of hypertension increased in relation to the number of risk alleles carried. When ten CHARGE SNPs for each trait were included in a joint meta-analysis with the Global BPgen Consortium (n = 34,433), four CHARGE loci attained genome-wide significance (P 5 × 10 8) for SBP (ATP2B1, CYP17A1, PLEKHA7, SH2B3), six for DBP (ATP2B1, CACNB2, CSK-ULK3, SH2B3, TBX3-TBX5, ULK4) and one for hypertension (ATP2B1). Identifying genes associated with blood pressure advances our understanding of blood pressure regulation and highlights potential drug targets for the prevention or treatment of hypertension.

Original languageEnglish (US)
Pages (from-to)677-687
Number of pages11
JournalNature genetics
Volume41
Issue number6
DOIs
StatePublished - Jun 1 2009
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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    Levy, D., Ehret, G. B., Rice, K., Verwoert, G. C., Launer, L. J., Dehghan, A., Glazer, N. L., Morrison, A. C., Johnson, A. D., Aspelund, T., Aulchenko, Y., Lumley, T., Köttgen, A., Vasan, R. S., Rivadeneira, F., Eiriksdottir, G., Guo, X., Arking, D. E., Mitchell, G. F., ... Van Duijn, C. M. (2009). Genome-wide association study of blood pressure and hypertension. Nature genetics, 41(6), 677-687. https://doi.org/10.1038/ng.384